The survival of motor neuron (SMN)
protein is mutated in patients with
spinal muscular atrophy (SMA). SMN is part of a multiprotein complex required for biogenesis of the Sm class of
small nuclear ribonucleoproteins (snRNPs). Following assembly of the Sm core domain, snRNPs are transported to the nucleus via
importin beta. Sm snRNPs contain a
nuclear localization signal (NLS) consisting of a
2,2,7-trimethylguanosine (TMG) cap and the Sm core. Snurportin1 (SPN) is the adaptor
protein that recognizes both the TMG cap and
importin beta. Here, we report that a mutant SPN construct lacking the
importin beta binding domain (IBB), but containing an intact TMG cap-binding domain, localizes primarily to the nucleus, whereas full-length SPN localizes to the cytoplasm. The nuclear localization of the mutant SPN was not a result of passive diffusion through the nuclear pores. Importantly, we found that SPN interacts with SMN, Gemin3, Sm snRNPs and
importin beta. In the presence of
ribonucleases, the interactions with SMN and Sm
proteins were abolished, indicating that snRNAs mediate this interplay. Cell fractionation studies showed that SPN binds preferentially to cytoplasmic SMN complexes. Notably, we found that SMN directly interacts with
importin beta in a GST-pulldown assay, suggesting that the
SMN complex might represent the Sm core
NLS receptor predicted by previous studies. Therefore, we conclude that, following Sm
protein assembly, the
SMN complex persists until the final stages of cytoplasmic
snRNP maturation and may provide somatic cell RNPs with an alternative NLS.